Human induced pluripotent stem cell-cardiomyocytes for cardiotoxicity assessment: a comparative study of arrhythmiainducing drugs with multi-electrode array analysis

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Na Kyeong Park Yun-Gwi Park Ji-Hee Choi Hyung Kyu Choi Sung-Hwan Moon Soon-Jung Park Seong Woo Choi
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제2호, 257~269쪽, 전체 13쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.03.01

국문 초록

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses. Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

목차

INTRODUCTION

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FUNDING

ACKNOWLEDGEMENTS

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REFERENCES

키워드

Arrhythmias cardiac Comprehensive in vitro proarrhythmia assay Electrophysiology Human induced pluripotent stem cells Myocytes cardiac